Interferon gamma produced by CD4+ T cells during malaria infection is known to be important for elimination of parasites from the host (also known as restriction). In preliminary studies, we have found that CD4+ T cells possess interferon-independent mechanisms of malaria parasite restriction, but the specific molecules involved remain unknown. We also find that phagocytes are critically important for control of acute infection, suggesting that CD4+ T cells may target myeloid cells such as macrophages through interferon-independent mechanisms. We have identified a candidate factor - macrophage colony stimulating factor - that is expressed by CD4+ T cells responding to malaria infection, and is consistent with the increase in macrophage numbers that occurs during malaria infection and their essentiality for anti-parasite activity. The proposed work will determine the role of macrophage colony stimulating factor in restriction of malaria parasites, and determine whether the fraction of this cytokine originating from CD4+ T cells plays a physiologically significant rol in this process. The studies have the potential to identify a significant new mechanism of host protection and a new role for helper T cells in contributing to the immunological control of malaria infection.